We hope to contribute to cancer therapy by improving cytokinetic methods for tumors and normal tissues and by judiciously applying them to several current biotherapeutic problems. Flow fluorometric methods which we have developed and successively applied in vitro will be extended to the rapid automatic assessment in vivo of the kinetics of unperturbed cells before the start of therapy and to the valid accurate measurement of cytokinetic changes throughout the course of therapy. These include: a) Our RCSi method (an automated analog of the traditional FLM method) in which cyclical progress of a pulse labeled cohort in a population of unperturbed cells is observed through a narrow window in S phase. b) Our computer analysis of multiple DNA distributions in which cell cycle transit times and dispersions are estimated quantitatively in perturbed populations and the perturbation is characterized. c) Several new approaches to the measurement of growth fraction in unperturbed or peturbed tissues. d) Cytochemical methods to discriminate among cell types and thus to extend flow analysis to heterogeneous cell populations. When the methods are ready for laboratory application we will use them to investigate several key cytokinetic issues in cancer biology and therapy. These include: a) The effect on growth fraction of tumor size and response to therapy. b) Proof-of-principle that therapy can indeed be optimized through the use of cytokinetic measurements. c) An analysis of the cytokinetic properties of micrometastases.